Purpose:
The importance of IL-6 activity in the development and normal function of the CNS is becoming increasingly evident. To identify consequences of IL-6 deficiency on the murine visual system, we examined retinal layer structure, retinal ganglion cell (RGC) health and functional visual capacity in adult (7 mo) wild type (WT) and IL-6 knockout (KO) mice.

Methods:
To determine impact on overall retinal structure, we used optical coherence topography (OCT) to measure the thickness of the retina as well as each retinal layer in WT and IL-6 KO mice. RGC health in these mice was ascertained using visual evoked potential (VEP), which measures N1 and P1 amplitude and latency of RGC based waveforms. To measure functional visual capacity, IL-6 WT and KO animals were subjected to Optokinetic Testing (OKT), which employs a rotating sine wave with variable spatial frequencies to measure visual spatial acuity threshold.

Results:
Based on OCT measurements, layer thickness in the IL-6 KO animals is compromised when compared to WT animals. Significantly thicker layers (p<0.05) in the IL-6 KO retina include the ganglion cell/neural fiber layer (RGC/NFL), inner plexiform layers (IPL), outer nuclear Layer (ONL) and outer plexiform layer (OPL). Interestingly, the inner nuclear layer (INL) in the IL-6 KO retina is the only layer that is significantly thinner compared to WT mice (p<0.05). Retinal ganglion cell activity measured by VEP was also found to be altered when compared to WT mice. The N1 amplitude of the IL-6 KO is 18.6% larger than in WT mice (p<0.05), while the N1 latency is 12.8% larger (p<0.001). No significant difference was found in the P1 amplitude or latency (p=0.43 & p=0.19 respectively). OKT testing determined the IL-6 KO mice have a 6% decrease in acuity threshold (p<0.05) when compared to IL-6 WT mice.

Conclusions:
Our data suggest that loss of IL-6 is associated with changes in retinal structure and inner retina activity. Interestingly, these changes seem to translate into a visual deficit, specifically, a decrease in visual acuity threshold. Overall, these data continue to support the hypothesis that IL-6 is important for normal function in the CNS.